The goal of the University of Alabama at Birmingham Core Center in Musculoskeletal Disorders (UAB-CCMD; Director: J. McDonald, MD) is to use a coordinated interdisciplinary approach to identify and characterize the key mechanisms underlying bone loss and regeneration and the systemic and local factors that regulate these processes, as a basis for the development of innovative therapeutic strategies. The primary disease focus is osteoporosis, but the effectiveness of the program is enhanced by the inclusion of investigators with expertise in periodontal disease, rheumatoid arthritis, and bioengineering. The UAB-CCMD has a research base of 33 investigators with expertise in regulation of bone cell differentiation and function; cell-cell and cell-matrix interactions; and growth factor and hormonal regulation of bone cells. Development of anabolic therapeutics will be facilitated by studies of transcriptional regulation of osteoblasts/adipocyte differentiation and the growth factor regulation of cell-cell and cell-matrix interactions, and the associated signal transduction pathways. Similarly, strategies based on the inhibition of osteopenic mechanisms will be facilitated by studies of the regulation of osteoblast function and proliferation, including regulation through the TNF/RANKL and Fas-mediated pathways, regulation of focal adhesion formation, and signal transduction mechanisms. Parallel develop of these fields, coordinated through the Administrative Core of the UAB-CCMD, is essential in targeting complex, multi-factorial bone diseases, and has led to the rapid formation of new collaborative efforts as the research unfolds. Several novel targets have been identified and their translational research is being promoted through a group of investigators with expertise in this filed, including analysis of the effects of current therapies and the development of vectors for gene therapy and as experimental tools. The UAB-CCMD Research Cores are essential to the success of this dynamic program: 1) a Human Bone Cell Production Core providing human osteoclasts and osteoblasts and key reagents for molecular experimentation; and 2) a Histomorphometry and Molecular Analysis Core providing state-of-the-art histological, histomorphometric, and highly sensitive cellular and tissue molecular probe technique. Three P&F studies have been competitively selected from 12 submissions: "The function of Smad3 in osteoblast differentiation", Xingming Shi, PhD; "Role of PYK2 and FAK in regulating osteoclastic bone resorption", Wen -Cheng Xiong, MD, PhD; and "Adhesion of osteoblasts to implant materials", Susan Bellis, PhD. The UAB-CCMD has the potential to make rapid and significant impact on the prevention and treatment of osteoporosis and related bone diseases.